This invention relates to the use of recombinant techniques to correct genetic deficiencies.
Hemophilia A, a bleeding disorder caused by a deficiency or abnormality of a particular clotting protein, Factor VIII-C, occurs in about 10-20 males in every 100,000. Afflicted individuals suffer episodes of uncontrolled bleeding and are treated currently with concentrates rich in Factor VIII-C derived from human plasma. Recombinant DNA technology has been proposed as useful for providing human Factor VIII-C purified from cultured cells as an alternative treatment for haemophiliacs (Toole et al., 1984, Nature 312:342).
Louis et al. (1988, Proc. Nat. Acad. Sci. USA 85:3150) implanted collagen-embedded mouse primary skin fibroblasts infected with a recombinant retrovirus containing human factor IX cDNA into the epidermis of mice, and detected human factor IX for 10-12 days in the sera.
Garver et al. (1987, Science 237:762) transplanted murine fibroblasts containing recombinant DNA encoding human .alpha..sub.1 -antitrypsin into the peritoneal cavity of nude mice, and detected human .alpha..sub.1 -antitrypsin in the sera and the epithelial surface of the lungs. Garver et al. observe that "the level of gene expression in target cells such as fibroblasts has generally been better than with primate bone marrow stem cells".